A large body of evidence implicates the mesocroticolimbic dopamine (DA) system, specifically the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc) in the neurobiology of natural (e.g. food) and artificial (e.g.drug) reinforcement, as well as motivational states associated with goal-seeking. However, relatively little has been established about how these two brain regions interact as a function of alterations in motivational state or reinforcer magnitude, or how such interactions modify the output of goal-direceted behavior. The current proposal is therefore intended to better understand the functional relationship between the mPFC and NAcc as it relates motivated behavior. The project has three specific aims. First, to build upon preliminary data obtained with c-Fos (a protein marker of neuronal activation) by employing in vivo microdialysis to further understand the interaction between mPFC and NAcc as a function of manipulations of motivational state and reinforcer magnitude. Second, to assess the effects of chemical inhibition and excitation of both mPFC and NAcc as it pertains to multiple behavioral indices of motivation (i.e. progressive ratio reponding for food reinforcement;conditioned approach behavior in an operant runway). Third, to assess the effects of D1/D2 antagonism in both mPFC and NAcc with respect to performance in the same behavioral assays. Understanding of the functional relationship between mPFC and NAcc as it pertains to motivation will provide crucial evidence about the processes by which the nervous system serves to organize behavior. Ample research in humans and in animals suggests that the brain regions under study in this proposal are crucial mediators of addiction, as well as other behavioral disorders with a motivational component. Thus, a complete understanding of how these brain areas function is necessary in order to fully address a number of important issues of public health.